Obesity and major depressive disorder (MDD) are increasingly common and pose enormous costs to individuals and society in the forms of health-care expenses, lost productivity, and personal distress. These disorders co-occur at rates greater than chance, though the specifics of how, among whom, and why remain unclear. This project will approach this issue in three different ways. In Aim #1, using a longitudinal prospective design, the degree to which earlier MDD predicts the onset of later obesity and the degree to which earlier obesity predicts the onset of later MDD will be examined during the period from childhood through early adulthood; this will enable us to identify periods of particula risk for the development of this comorbidity. In Aim #2, associations between these disorders within families will be examined by determining how MDD and obesity in parents are associated with risk for these same disorders in late-adolescent offspring. In Aim #3, possible causal associations between MDD and obesity will be investigated using longitudinal co-twin control and co-twin difference designs. In the co-twin control designs, twin pairs in which one has the disorder of interest (e.g., MDD) and the other does not are followed over time to examine the development of another disorder (e.g., obesity). If the twin with the earlier disorder is at increased risk for the later disorder compared to the co-twin without the disorder, this points to the earlier disorder creating an experiential context with a causal influence on the development of the later disorder. If the twin without the initial disorder shows risk for the later disorder tat is equivalent to that of the co-twin with the initial disorder, this points to the likelihood that oneis not part of the causal chain for the development of the other. Discordant monozygotic twins are particularly informative because they share both the same genetic make-ups and rearing environments. Co-twin difference analyses extend the co-twin control design by utilizing these same principles to maximize statistical power by using the entire sample and dimensional measures of body mass index and MDD symptoms. To address these Aims, archival data from the Minnesota Twin Family Study will be used. This is a community-based sample of twins and their parents, with clinical assessments of MDD and obesity every 3-4 years from ages 11 to 29 (up to 6 time points) in the youth, as well as clinical assessments of MDD and obesity in their parents. The youth sample sizes at different ages range from 2,510 to 3,762, with follow-up rates above 87% at each assessment. In addition, data are available on 3,622 parents. To maximize both public health impact and statistical power, both dimensional and categorical analyses are planned. By elucidating longitudinal associations between MDD and obesity, the associations between these disorders within families, and the potential causal paths between these disorders, this project has a high likelihood of yielding an improved understanding of these associations.